Although Candida albicans normally colonizes in the human body, normal individuals are usually resistant to infection therewith and seldom suffer from systemic infectious disease caused thereby. Even in normal individuals, however, this fungus can cause local infectious disease; in females, particularly in pregnant women, it can cause vaginal candidiasis. On the other hand, in humans rendered immunocompromised as a result of administration of an anticancer agent for treatment of a cancer, such as leukemia, administration of an immunosuppressant for organ transplantation, infection with AIDS, or the like, this fungus can cause systemic infectious diseases affecting various internal organs. Furthermore, this fungus represents the most common fungal allergen as a cause of allergosis. In addition, most humans are immunologically sensitized with the normally colonizing fungus Candida albicans, possess antibodies against its components, and have acquired cellular immunity thereto.
Many of the Candida albicans antigens are cell wall components on the cell surface, mainly polysaccharides, such as mannan and glucan, mannan and its conjugate with protein being particularly predominant. In addition, in sera from patients with Candida albicans infection or those with allergy, antibodies against the intracellular components enolase, HSP90 (heat shock protein 90), phosphoglycerate kinase, or alcohol dehydrogenase are detected, in addition to the antibodies against the aforementioned cell wall components.
Fungi of the genus Candida other than Candida albicans, for instance, C. tropicalis and C. glabrata, cause infectious disease mainly in immunocompromised hosts. Fungi other than those of the genus Candida, for instance, fungi of the genera Aspergillus, Penicillium, and Alternaria, also occur widely in our environment and are very close to mammals, including humans. Although these fungi are yeast-like or mycelial in the cellular morphology to grow, their cellular structures are basically similar to each other, all having a surface layer surrounded by a thick cell wall. Although the chemical structure of the cell wall varies to some extent depending on kind of fungus, the cell wall components mainly comprise polysaccharides, such as mannan, glucan, and chitin. In addition, the proteins and other components in the cell membrane and cytoplasm surrounded by the cell wall are also basically similar to each other. Many of these fungi also cause infectious disease in immunocompromised hosts, or serve as causes of allergy.
As pathogenic factors and allergens in fungus-involved disease, some antigen molecules derived from fungus have been isolated and identified. Isolation and identification of these antigen molecules are usually achieved using sera from fungus-sensitized mammals; the most common of such antigen molecules that have been identified so far are the cell wall components surrounding the fungal surface layer. In addition to the above components, a number of antigen molecules have been isolated and identified, and are under investigation for the purposes of diagnosis and therapy. It should be noted, however, that not all antigens reactive to antibodies retained in fungus-sensitized state act effectively in infectious disease or allergosis.
An object of the present invention is to provide a novel antigenic protein useful in the treatment and diagnosis of diseases caused by fungi including Candida albicans. Another object of the present invention is to provide a nucleic acid encoding the antigenic protein. Still another object of the present invention is to provide a vector comprising the nucleic acid, and a transformant resulting from transformation with the vector. Still another object of the present invention is to provide a method for producing the antigenic protein of the present invention, wherein the method comprises culturing the transformant. A further object of the present invention is to provide a pharmaceutical composition and diagnostic composition, each comprising the antigenic protein or nucleic acid of the present invention.